Previously, classic genetic screens have been used to identify genes involved in the C. elegans development. In one example, inhibition of mitochondrial respiratory chain genes such as NADH ubiquinone oxidoreductase and ATP synthase in C. elegans larva was found to impair larval development and cause arrest in the third larval stage (see, e.g., Tsang et al., JBC 276:33240-33246 (2001)). In other examples, classical genetic screens have been used to identify C. elegans genes involved in a variety of processes, including dauer formation, and embryonic development. Some of these genes, for example the daf-2 and daf-16 genes, have been implicated in the regulation of lifespan see, e.g., Kenyon et al., Nature 366:461-464 (1993); Morris et al., Nature 382:536-539 (1996); Kimura et al., Science 277:942-946 (1997); Paradis et al., Genes Dev. 12:2488-2498 (1998); Paradis et al., Genes Dev. 13:1438-1452 (1999); Off & Ruvkun, Mol. Cell 2:886-893 (1998); Guarente & Kenyon, Nature 408:255-262 (2000); Ogg et al., Nature 389:994-999 (1997); and Lin et al., Science 278:1319-1322 (1997)).
Classical genetic screens are frequently time consuming, both in identification of interesting mutants and in cloning a gene associated with a mutation. Classical genetic screens can include labor intensive backcrosses to eliminate mutations unlinked to the phenotype of interest. Classical genetic screens also may require the extra step of cloning the gene of interest, by complementation of the mutation.
Many different genes likely regulate the process of aging in eukaryotes and their identification will aid in understanding the process. Regulation of biological processes is frequently conserved between divergent organisms. For example, cell cycle proteins and their mechanism of action are conserved between organisms as divergent as yeast and humans. Thus, regulatory mechanisms identified in a genetically tractable organism can be used to predict and identify homologous genes and gene products that regulate similar biological processes in higher eukaryotes. However, even in genetically tractable organisms, such as C. elegans, classical genetic methods are frequently labor intensive and cumbersome for identification of interesting mutants and for isolation of a gene of interest. The present invention solves these and other problems.